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Biomedical subjects

H Mitsuhashi

Publications and source records attributed to H Mitsuhashi.

At least 19 recordsLinked to original sources
PubMed1996

Administration of truncated secretory leukoprotease inhibitor ameliorates bleomycin-induced pulmonary fibrosis in hamsters.

The purposes of this study were to investigate the effect of our recently developed truncated secretory leukoprotease inhibitor (SLPI) on bleomycin (BLM)-induced lung injury and fibrosis in hamsters, which is widely used as a model of interstitial pulmonary fibrosis, and to assess the possible involvement of neutrophil elastase in the pathogenesis of pulmonary fibrosis. The fibrosis model was prepared by administration of BLM (10 mg/kg) intratracheally to hamsters. The truncated SLPI was administered at a dose 5 or 15 mg/kg intraperitoneally twice a day only for 10 d starting from the time of BLM administration. BLM administration resulted in decreases in body weight and survival rate. Elastase activity in the supernatant of bronchoalveolar lavage (BAL) fluids was increased at 3 and 7 d after BLM administration in parallel with the increase in the number of neutrophils in the fluids. Histopathologically, at 14 and 28 d after BLM administration, diffuse thickening and fibrosis of alveolar walls with marked cell infiltration and severe distortion of alveolar structure, including honeycomb lung, were observed to have occurred. In this model, the decreases in body weight and survival rate and the increase in elastase activity were inhibited by the truncated SLPI dose-dependently, and pulmonary fibrosis was significantly ameliorated by the administration of this shortened form of SLPI. These results suggest that neutrophil elastase may be implicated in the pathogenesis of BLM-induced pulmonary fibrosis and that the truncated SLPI might be a promising therapeutic in the treatment of interstitial pulmonary fibrosis.

Animals↗
PubMed1996

Aerosolized human neutrophil elastase induces airway constriction and hyperresponsiveness with protection by intravenous pretreatment with half-length secretory leukoprotease inhibitor.

This study was designed to determine the effects of inhaled human neutrophil elastase (HNE) on airway constriction and airway responsiveness, and to examine the protection by an intravenous recombinant half-length secretory leukoprotease inhibitor, r1/2SLPI in guinea pigs. Aerosol inhalation of HNE (250 microgram/ml, for 3 min) caused a transient but significant airway constriction, in which lung resistance (RL) increased from 194 +/- 18 (mean +/- SEM) to 461 +/- 42 cm H2O/L/s (p < 0.001). Thirty minutes after the end of HNE inhalation, airway responsiveness to intravenous 5-hydroxytryptamine (5-HT) was significantly increased. The provocative dose causing a 200% increase in RL (PD200) was significantly decreased from 10.0 +/- 1.2 to 6.5 +/- 0.8 microgram/kg (p < 0.001). Forty-five minutes after the end of HNE inhalation, total cells in bronchoalveolar lavage fluid (BALF) were significantly increased (p < 0.05). Histologic study of intrapulmonary bronchi demonstrated an acute inflammatory response characterized by damage to the epithelium, airway obstruction by mucus plugs, and recruitment of mononuclear and polymorphonuclear cells to the bronchial epithelium. r1/2SLPI (30 mg/kg) injected 5 min before the initiation of HNE inhalation significantly inhibited the airway constriction (p < 0.05), the airway hyperresponsiveness (p < 0.01), and the increase of cells in BALF (p < 0.05). The present data suggest that HNE plays a role in the induction of airway constriction and airway hyperresponsiveness in various inflammatory lung diseases with pulmonary neutrophil infiltration, such as chronic obstructive pulmonary diseases (COPD) and possibly bronchial asthma. r1/2SLPI may be useful as an antiprotease treatment.

Aerosols↗
PubMed1994

A rare portosystemic shunt detected by MRI and diagnosed by dynamic liver scintigraphy with Tc-99m phytate.

Although various types of portosystemic shunts with portal hypertension have been widely reported, a collateral circulation near the pancreas head is rare. The authors report a case of a rare portosystemic shunt surrounding the pancreatic head, which was diagnosed by dynamic liver scintigraphy using Ikoma's scintigraphic criteria for the presence of portosystemic shunts. According to these criteria, abnormal accumulation of radioactivity at various abdominal sites (not identified on static images after the dynamic study) on 6 or more continuous frames of 5-second intervals (i.e., for 30 seconds or more after the arterial phase) indicates the presence of a portosystemic shunt. If liver scintigraphy is performed on a patient with portal hypertension, the dynamic study is valuable in the detection and diagnosis of a portosystemic shunt.

Aged↗
PubMed1994

Increased excretion of urinary transforming growth factor beta in patients with focal glomerular sclerosis.

The urinary transforming growth factor beta (TGF-beta) excretion was measured in 33 patients including 10 with systemic lupus erythematosus (SLE), 8 with focal glomerular sclerosis (FGS), 9 with IgA nephropathy (IgAN), and 6 with membranous nephropathy (MN), and in 7 healthy subjects by enzyme-linked immunosorbent assay using a monoclonal antibody specific for TGF-beta 1 + 2 + 3. A significantly increased urinary TGF-beta excretion was observed in FGS patients (555.5 +/- 458.4 ng/mg Cr) as compared with normal controls (46.9 +/- 43.9 ng/mg Cr) (p < 0.05) and a relative increase in SLE patients (96.4 +/- 58.2 ng/mg Cr) and a decrease in MN patients (24.8 +/- 13.3 ng/mg Cr). In contrast, there was no difference in TGF-beta excretion between IgAN patients (54.1 +/- 37.4 ng/mg Cr) and normal controls. A correlation between the amount of proteinuria and TGF-beta was not found. As has been previously demonstrated in experimental studies, TGF-beta may play a similar role in human glomerular diseases. The results obtained in this study raised the possibility that extracellular matrix might be produced by glomerular cells in vivo under the control of TGF-beta and that TGF-beta might act as a stimulator for the development of glomerulosclerosis.

Adolescent↗
PubMed1994

Combined treatment with cyclophosphamide and prednisolone can induce remission of nephrotic syndrome in a patient with renal amyloidosis, associated with rheumatoid arthritis.

A 67-year-old woman, who had been diagnosed with classical rheumatoid arthritis (RA), was admitted to our hospital because of massive proteinuria. Biopsy of the kidney revealed deposition of amyloid fibrils in the subepithelial and subendothelial spaces of the glomerular capillary walls. Though the treatment with prednisolone and dipyridamole against nephrotic syndrome and amyloidosis due to RA was not effective, cyclophosphamide, which was added after tapering of prednisolone, was able to induce remission of nephrotic syndrome after two years. The levels of CRP and serum amyloid A protein (SAA) returned to within the normal limits. As the impairment of renal function is thought to be due to deposition of amyloid supplied from the precursors of amyloid fibrils filtered from the general circulation in RA patients, remission of nephrotic syndrome might result from the suppression of production of SAA or removal of amyloid fibrils. Cyclophosphamide, which has the potential both to suppress disease activity in RA and to produce degradation of amyloid fibrils in glomeruli, may be useful against renal or systemic amyloidosis complicated by RA.

Aged↗
PubMed1994

Henoch-Schönlein purpura in rheumatoid arthritis.

This is the first report of Henoch-Schönlein purpura associated with permanent joint damage due to rheumatoid arthritis, which was observed in 3 of the 10 adults we treated for Henoch-Schönlein purpura since 1974. Each of 3 women had been admitted with palpable purpura of the lower extremities. The diagnosis was based on various findings including arthralgia, stiffness, and/or swelling of the joints, and on the results of radiographic, immunofluorescence and other studies. Renal biopsy revealed slight mesangial proliferation in 2 of the patients. The nephropathy did not deteriorate following discharge. However, bilateral swelling of the wrists with destructive joint changes was subsequently observed on radiographs in all patients. Since 2 patients showed positivity for human leukocyte antigen DR4, this antigen may have been a genetic factor in the joint disease in these patients.

Adult↗
PubMed1994

[Thrombotic thrombocytopenic purpura (TTP) with a low level of apolipoprotein A-I (Apo A-I) which responded to combination of vincristine and beraprost].

A 51-year-old man was admitted to the psychiatric ward because of increasing confusion and irrational behavior. He was later transferred to our department due to anemia and thrombocytopenia. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made based on the presence of thrombocytopenic purpura, microangiopathic hemolytic anemia, neurological symptoms and fever. Corticosteroids, plasma exchange (PE), dextrans, dipyridamole and vincristine (VCR) were given without satisfactory response. Beraprost sodium was prescribed followed by a dramatic improvement and complete remission. A number of reports indicated that prostacyclin metabolism was involved in the pathogenesis of TTP. Recently Apo A-I was identified to be a prostacyclin-stabilizing factor, which was initially low in this patient. If patients do not respond to either PE or VCR, consideration should be given to treatment with beraprost, especially when the level of Apo A-I is low.

Apolipoprotein A-I↗
PubMed1994

[A case report of giant epidermoid in the temporal lobe: considerations of the occurrence of intramedullary epidermoids].

A case of giant epidermoid which was mainly located in the right temporal lobe was presented. The intracranial epidermoid is commonly located in the CSF space, such as the cerebello-pontine (C-P) angle, parasellar region, middle cranial fossa and ventricles. The intramedullary epidermoid is extremely rare. We report the case of a 51-year-old female suffering from generalized convulsions. Having fallen into a semicoma due to the convulsions, she was referred to our department on August 5, 1992. Neurological examination revealed slight dementia but no other deficits. The tumor was mainly located in the temporal lobe but communicated with the CSF space of C-P angle through a narrow channel shown on MRI. She underwent an operation for tumor removal and left the hospital with no neurological deficits. Several cases of intracranial intramedullary epidermoid have been reported in the literature, but none of them proved to be completely intramedullary. On operation or on CT and MRI, all of them were shown to communicate with the CSF space. The possible occurrence of an epidermoid from medullary substance was discussed.

Brain Diseases↗
PubMed1993

Effect of Pinellia ternata tuber on the efferent activity of the gastric vagus nerve in the rat.

Effect of intraduodenal infusion with the hot aqueous extract of Pinellia ternata tuber on the efferent discharges in the gastric branch of the vagus nerve was observed in the anesthetized rat. The infusion of the extract in doses of 2-15O mg per animal (c.a. 300 g, b.wt.) resulted in a dose-related increase in efferent activity of the vagal gastric nerve. The enhancement of the nerve activity following administration of 150 mg of this substance lasted longer than 90 min. It was observed that the suppressive effect on vagal gastric activity due to apomorphine and copper sulfate was antagonized by prior administration of the extract. From these observations it is suggested that Pinellia tuber acts as a facilitatory agent on gastric function.

Animals↗
PubMed1993

Urine glycosaminoglycans and heparan sulfate excretions in adult patients with glomerular diseases.

We measured the concentrations of urine glycosaminoglycans (GAG) by the modified dimethylmethylene blue method and the concentration of urine heparan sulfate (HS) by enzyme-linked immunosorbent assay (ELISA) in patients with various glomerular diseases. The GAG/creatinine(Crea) ratios in patients with IgA nephropathy (mean +/- SD, 0.31 +/- 0.056) and membranous nephropathy (0.41 +/- 0.115) were significantly greater than in healthy controls (0.18 +/- 0.045). Urine GAG/Crea ratios in minimal change nephrotic patients increased during remission (0.38 +/- 0.102) and decreased to normal values during the nephrotic stage (0.25 +/- 0.088). In contrast, urine HS/Crea ratios in patients with minimal change nephrotic syndrome decreased during remission (0.0069 +/- 0.0029) and increased markedly during the nephrotic period (0.047 +/- 0.0007 versus controls 0.0158 +/- 0.0046). Serial measurement in three minimal change nephrotic patients showed the similar change for the HS/Crea ratio and urine albumin excretion in the course of steroid therapy. The loss of HS from the glomerular basement membrane (GBM) may therefore be related to the pathogenesis of increased albumin excretion and measurement of urine HS excretion may be helpful for studying metabolism in renal disease, especially in patients with minimal change lesions.

Adult↗
PubMed1992

Gomisin A inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Gomisin A, isolated from the fruits of Schisandra chinensis, is one of the dibenzocyclooctadiene lignans. Application of 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 microgram/ear), a tumor-promoting agent, to the ears of mice induces inflammation. Among seven dibenzocyclooctadiene lignans assayed, gomisin A, gomisin J, and wuweizisu C inhibited the inflammatory activity induced by TPA in mice. The ED50 of these compounds for TPA-induced inflammation was 1.4-4.4 mumol. Gomisin A, with an ED50 of 1.4 mumol, showed the strongest inhibitory effect. Furthermore, at 5 mumol/mouse, it markedly suppressed the promotion effect of TPA (2.5 micrograms/mouse) on skin tumor formation in mice following initiation with 7,12-dimethylbenz[a]anthracene (50 micrograms/mouse). It is assumed that the inhibition of tumor promotion by gomisin A is due to its anti-inflammatory activity.

Animals↗
PubMed1991

Ion-sparing diuresis by 2,3-dibenzylbutane-1,4-diol, a synthetic mammalian-lignan derivative.

Diuretic properties of a synthetic lignan, 2,3-dibenzylbutane-1,4-diol (hattalin), and a naturally occurring arctigenin were examined in BALB/c male mice and Wistar male rats. Intra peritoneal administration of hattalin (50 mg/kg) in mice increased urine volume by 1.7-3.1 fold that of placebo-treated animals 40-260 min after administration (p less than 0.05 vs control). In contrast, 100 mg/kg of arctigenin had no effect on urine volume in mice. Hattalin (100 mg/kg), arctigenin (100 mg/kg), or furosemide (50 mg/kg) as a positive control was administered orally to rats, and accumulated urine volume was measured for up to 6-12 h. The urine volume of animals administered with hattalin showed 1.4-1.5 fold that of placebo-treated animals after 2-6 h of administration (P less than 0.05, n = 10). On the other hand, arctigenin showed no significant effect on urine volume for up to 12 h after administration (n = 8). The urine volume in animals administered with furosemide (n = 10) was 2.0-3.0 fold that of placebo-treated animals (P less than 0.01). Furosemide increased total Na+, K+, or Cl- excretion by 1.9, 1.8 or 2.2 fold, respectively, when compared with placebo-treated controls (P less than 0.01), whereas hattalin decreased Na+ excretion by 3.6 times (P less than 0.01), K+ excretion by 1.4 times (not significant), and Cl- excretion by 3.1 times (P less than 0.01). Serum Na+ and K+ levels did not change in both furosemide- and hattalin-administered rats, however, serum Cl- levels in these animals significantly decreased (P less than 0.01) when compared with controls. The results suggest that the diuretic property of hattalin is due to a novel mechanism which is different from that of furosemide or other diuretics modifying the ion-exchange at the uriniferous tubules.

Animals↗
PubMed1991

Nine phenethyl alcohol glycosides from Stachys sieboldii.

Three new phenethyl alcohol glycosides together with six known compounds have been isolated from the leaves of Stachys sieboldii. On the basis of chemical and spectral analyses, the structures of three new compounds named stachysosides A, B and C have been established as 2-(3,4-dihydroxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E-caffeoyl-beta-D-glucopyranoside, 2-(3,4-dihydroxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E-feruloyl-beta-D-glucopyranoside and 2-(3-hydroxy-4-methoxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E- feruloyl-beta-D-glucopyranoside, respectively.

Carbohydrate Sequence↗
PubMed1991

Blood viscosity measurement for screening of affecting blood circulation.

An in vitro screening test for drugs that decrease blood viscosity was carried out on many pharmacologically active compounds such as Ca-antagonists, alpha-antagonists, beta-antagonists, alpha, beta-antagonists, alpha-agonists, beta-agonists, alpha, beta-agonists, autacoids and others. The results revealed that various types of microcirculatory-improving drugs, vasodilators, and antagonists decreased blood viscosity, while the agonists and autacoids had no significant effect. These findings suggest that this assay is useful for screening compounds related to hemorheology.

Animals↗
PubMed1991

Synthesis and protective effect of 1,3,5-triazine derivatives, leukotriene C4 antagonist, on HCl.ethanol-induced gastric lesions in rats.

2,4-Diamino-[E]-6-[2-(3-pyridyl)ethenyl]-1,3,5-triazine (3a), leukotriene C4 (LTC4) antagonist, was found to possess a protective effect on HCl.ethanol-induced gastric lesions. Analogues of 3a were synthesized and evaluated for the effect as well as antagonistic activity against LTC4-induced contraction. Seven compounds (3a-d, f-h) exhibited a potent protective effect on gastric lesions which was considered to be based on the antagonistic activity against LTC4. The structure-activity relationships of the derivatives (3a-k) are discussed.

Animals↗
PubMed1991

[Studies on the metabolic fate of gomisin A (TJN-101). I. Absorption in rats].

Gomisin A (TJN-101) is one of the lignan components isolated from Schisandra Fruits and expected to have some efficacies in clinical treatment of hepatitis. The serum concentrations of TJN-101 and Met. B, which was identified as a demethylenated substance and one of the major metabolites of TJN-101 in rats, were investigated. After intravenous administration at doses of 1.6, 4.0 and 10 mg/kg of body weight, the serum concentration of TJN-101 decreased biphasically, and the terminal elimination half-life at each dose was about 70 min. Dose-dependency was observed for the area under the concentration-time curve (AUC). On the other hand, the serum concentration of TJN-101 increased rapidly and reached maximum within 15 to 30 min when administered orally. This result was supported by the in situ roop method. The Cmax and the AUC values were not exactly dose-dependent, but the values increased with a dose-up of TJN-101. The biotransformation of TJN-101 to Met. B, was very rapid in both intravenous and oral administrations. The AUC value of Met. B after oral administration of TJN-101 at a dose of 1.6 mg/kg was relatively larger than any other dosages. It suggested that TJN-101 was extensively underwent the first pass effect in rats. More than 80% of TJN-101 was bound with rat serum protein in vitro and in vivo. Therefore, it seems to be necessary to pay attention when it was administered concurrently with high protein binding drugs.

Administration, Oral↗
PubMed1990

The destructive effects of sclerosant ethanolamine oleate on mammalian vessel endothelium.

Ethanolamine oleate (EO) used widely in sclerotherapy against esophageal varices was studied for its pharmacological effect on blood coagulation and vascular damage in animals. Blood coagulation was completely inhibited by EO at a concentration of 0.31%. EO destroyed the endothelial cells of the vessel of dog and rat within one minute after injection into the vessels. An accumulation of fibrin and platelets on the surface of the damaged vessel was observed electron microscopically. Mural thrombus was formed in a few hours and the thrombus occluded the blood stream in the vein. From these animal experiment, intravasal injection of EO was considered to cause the disappearance of varices by the following two processes: collapse of varices because of occlusion of the blood stream and shrinking of the obstructed thrombus through organization.

Adult↗